Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study.

Autor: Knorr U; Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: ulla.knorr@regionh.dk., Simonsen AH; Danish Dementia Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Nilsson J; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden., Brinkmalm A; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Zetterberg H; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, University College London, Queen Square, London, United Kingdom; UK Dementia Research Institute University College London, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., Blennow K; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China., Knudsen MB; Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark., Forman J; Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark., Hasselbalch SG; Danish Dementia Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark., Kessing LV; Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2024 Aug 01; Vol. 358, pp. 250-259. Date of Electronic Publication: 2024 May 07.
DOI: 10.1016/j.jad.2024.05.034
Abstrakt: Background: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections.
Methods: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year. Synaptic proteins encompassing neuronal pentraxins (NPTX)1, NPTX2, and NPTX-receptor, 14-3-3 protein family epsilon, and zeta/delta, activating protein-2 complex subunit beta, synucleins beta-synuclein and gamma-synuclein, complexin-2, phosphatidylethanolamine-binding protein 1, rab GDP dissociation inhibitor alpha, and syntaxins 1B and 7 were measured in CSF using a microflow liquid chromatography-mass spectrometric multiple reaction monitoring set-up. Biomarker levels were compared between BD and HC and in BD before, during, and after mood episodes.
Results: The synaptic proteins revealed no statistically significant differences between BD and HC, neither at baseline, one-year follow-up, or in terms of changes from baseline to follow-up. Moreover, the CSF synaptic protein levels in patients with BD were unaltered compared to baseline when they stabilized in euthymia following an affective episode and at one-year follow-up.
Limitation: It is uncertain what the CSF biomarker concentrations reflect since we yet do not know the mechanisms of release of these proteins, and we are uncertain of what increased or decreased levels reflect.
Conclusion: This first-ever investigation of a panel of CSF protein biomarkers of synaptic dysfunction in patients with BD and HC individuals found no statistically significant differences cross-sectionally or longitudinally.
Competing Interests: Declaration of competing interest UK and JF are appointed as associated professors at the University of Copenhagen. AHS is funded by Absalonfonden. MBK is appointed as a statistical consultant for this project. His salary is covered by a grant from the Overlæge Dr. Med. Einar Geert- Jørgensen og Hustrus Legat. SGH and LVK are appointed as professors at the University of Copenhagen and Mental Health Services - Capital Region of Denmark. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. KB is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF- 742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236).
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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